Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1998-09-08
2001-03-20
Le, Long V. (Department: 1641)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S091100, C435S287200, C436S501000, C205S091000, C205S092000, C205S118000, C205S122000, C205S340000
Reexamination Certificate
active
06203985
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to analysis of molecular samples.
More particularly, the present invention relates to fabrication of molecular analyzers and analysis of bio-molecule samples.
2. Prior Art
Identification of molecular structure has become very important in many industries. In particular, biological molecules such as nucleic acids and proteins are analyzed to form the basis of clinical diagnostic assays. The procedures utilized often involve large numbers of repetitive steps which consume large amounts of time. With the advent of large projects such as the human genome project, faster and less complex techniques are required.
Simpler and quicker analysis of molecules has been provided by the development of devices often referred to as bio chips, which are arrays of test sites formed on a substrate. Each of the plurality of test sites includes probes therein to bond with target molecules from samples applied to the device. The binding of a molecule to a probe is noted, thereby identifying the molecule.
While increasing the speed and efficiency of analyzing samples, the arrays of test sites must still immobilize specific bio-molecules on a solid surface to act as probes. Conventionally, placing bio-molecules as probes on specific test sites is time consuming, expensive, often lacks the desired accuracy and does not meet the desired size constraints. Placement of bio-molecules for probes is conventionally accomplished by in-situ synthesis using photolithography, which is very labor intensive with unsatisfactory accuracy, mechanical spotting, which is a slow process with the smallest test site size limited by the nature of the process, or chemical ink jetting, having an inaccuracy similar to in-situ synthesis and test site size limits similar to mechanical spotting.
Furthermore, once fabrication has been completed, a method for the detection of the bonding of the probe with a target molecule must be provided. There are many techniques for determining which test sites have molecules bonded to them including autoradiography, optical detection (fluorescence) and electronic detection. The use of monolithic devices with an array of test sites generally require externally accessible terminals for each test site. As the number of test sites in an array is increased, the complexity of providing and making contact with the terminals for each test site becomes increasingly difficult and burdensome.
It would be highly advantageous, therefore, to remedy the foregoing and other deficiencies inherent in the prior art.
Accordingly, it is an object of the present invention to provide a new and improved apparatus for analyzing molecules and method for fabrication and use thereof.
Another object of the present invention is to provide a method and apparatus for analyzing molecules using wireless contacts for a spatially addressable array of test sites.
And another object of the present invention is to provide a method and apparatus for analyzing molecules which is fast and efficient.
A further object of the present invention is to provide a method and apparatus for analyzing molecules wherein the light source array is used to fabricate the test sites and is therefore self aligned with the test sites for use as the excitation source in optical detection.
Still another object of the present invention is to provide a method and apparatus which can include more test sites than prior art methods using wire connections in the same area.
SUMMARY OF THE INVENTION
Briefly, to achieve the desired objects of the instant invention, in accordance with a preferred embodiment thereof, provided is a method of fabricating a bio-molecule analyzer including the steps of providing a photoconductive layer of material having a layer of electrically conductive material on a first surface thereof and a test site on an opposing second surface thereof. A solution containing a plurality of probe molecules is placed in electrical contact with the test site and an electrical potential is connected between the solution and the layer of electrically conductive material. A beam of light is directed through a portion of the photoconductive layer of material to complete an electrical circuit between the layer of electrically conductive material and the solution through the portion of the photoconductive layer and the test site. In this manner, probe molecules in the solution are attracted to and bound to the test site, which is coupled into the electrical circuit by the beam of light.
Also provided is a bio-molecule analyzer including a photoconductive layer of material, having a layer of electrically conductive material on a first surface thereof, mounted on an array of addressable light sources. A plurality of test sites on an opposing second surface of the photoconductive layer of material are defined by the plurality of light sources. A solution containing a plurality of bio-molecules is received by the analyzer in electrical contact with the plurality of test sites. An electrical potential is connected between the solution and the layer of electrically conductive material. The array of addressable light sources emit beams of light through a plurality of portions of the photoconductive layer of material to define the test sites and complete electrical circuits between the layer of electrically conductive material and the solution through the plurality of portions of the photoconductive layer and the plurality of test sites.
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patent: 5667667 (1997-09-01), Southern
patent: 5810989 (1998-09-01), Krihak et al.
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patent: 9852042 (1998-11-01), None
“The Light-Addressable Potentiometric Sensor: Principles and Biological Applications”, John C. Owicki et al., Annu. Rev. Biophys. Biomol. Struct., 1994, pp. 87-113.
“Light Addressable Potentiometric Semiconductor Biosensor”, H.M. McConnel et al., Extended Abstracts/Electrochemical Society, Abstract No. 1679, p. 2272.
Foley Barbara M.
Gallagher Sean
Hartman Davis H.
Jiang Wenbin
Yu Huinan
Koch William E.
Le Long V.
Motorola Inc.
Parsons Eugene A.
Pham Minh-Quan K.
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